细胞内积累研究是金属药物开发的关键步骤，但常常会得到可变的结果。因此，我们旨在研究不同的方案，以寻求高效和可重复的溶解癌细胞的方法，以确定细胞裂解物中的蛋白质含量和鲁铂抗癌配合物[氯化（8-氧喹啉基）（η6-对二甲苯）二茂铷（II）]（[Ru(cym)(HQ)Cl]）进入细胞的研究。物理裂解方法渗透和超声波裂解法被选择与化学裂解法放射免疫沉淀试验缓冲液（RIPA）进行比较。基于蛋白质含量和用电感耦合等离子体质谱（ICP-MS）测定的裂解物中总鲁铂含量，RIPA缓冲液是最高效的裂解方法。对塑料吸附阴性对照的测量结果显示，RIPA缓冲液裂解样品中较高的鲁铂含量可能是由于与渗透和超声波裂解相比，RIPA缓冲液从塑料孵育板中提取了更多的鲁铂。总体上，我们发现选择裂解方法应与所需信息相匹配，我们建议最少干扰的渗透法可能是处理不稳定药物-生物分子复合物的最佳选择。对于旨在测量鲁铂配合物整体细胞摄取的实验，发现差异很小。© 2023年作者。由牛津大学出版社出版。

Intracellular accumulation studies are a key step in metallodrug development but often variable results are obtained. Therefore, we aimed here to investigate different protocols for efficient and reproducible lysis of cancer cells in terms of protein content in lysates and in cell uptake studies of the Ru anticancer complex [chlorido(8-oxyquinolinato)(η6-p-cymene)ruthenium(II)] ([Ru(cym)(HQ)Cl]). The physical lysis methods osmosis and sonication were chosen for comparison with chemical lysis with the radioimmunoprecipitation assay buffer (RIPA). Based on the protein content and the total Ru accumulated in the lysates, the latter determined using inductively-coupled plasma mass spectrometry (ICP-MS), RIPA buffer was the most efficient lysis method. Measurements of plastic adsorption blanks revealed that the higher Ru content determined in the RIPA buffer lysis samples may be due a higher amount of Ru extracted from the plastic incubation plates compared with osmosis and sonication. Overall, we found that the choice of lysis method needs to be matched to the information sought and we suggest the least disruptive osmosis method might be the best choice for labile drug-biomolecule adducts. Minimal differences were found for experiments aimed at measuring the overall cell uptake of the Ru complex.© The Author(s) 2023. Published by Oxford University Press.